D1 and D2 medium spiny neurons in the nucleus accumbens core have distinct and valence-independent roles in learning

Jennifer E. Zachry, Munir Gunes Kutlu, Hye Jean Yoon, Michael Z. Leonard, Maxime Chevée, Dev D. Patel, Anthony Gaidici, Veronika Kondev, Kimberly C. Thibeault, Rishik Bethi, Jennifer Tat, Patrick R. Melugin, Atagun U. Isiktas, Max E. Joffe, Denise J. Cai, P. Jeffrey Conn, Brad A. Grueter, Erin S. Calipari

Research output: Contribution to journalArticlepeer-review

Abstract

At the core of value-based learning is the nucleus accumbens (NAc). D1- and D2-receptor-containing medium spiny neurons (MSNs) in the NAc core are hypothesized to have opposing valence-based roles in behavior. Using optical imaging and manipulation approaches in mice, we show that neither D1 nor D2 MSNs signal valence. D1 MSN responses were evoked by stimuli regardless of valence or contingency. D2 MSNs were evoked by both cues and outcomes, were dynamically changed with learning, and tracked valence-free prediction error at the population and individual neuron level. Finally, D2 MSN responses to cues were necessary for associative learning. Thus, D1 and D2 MSNs work in tandem, rather than in opposition, by signaling specific properties of stimuli to control learning.

Original languageEnglish
Pages (from-to)835-849.e7
JournalNeuron
Volume112
Issue number5
DOIs
StatePublished - 6 Mar 2024

Keywords

  • aversion
  • calcium imaging
  • fear conditioning
  • motivation
  • reinforcement learning
  • striatum

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